GEO DataSets

(Submitter supplied) We discovered potent small molecule inhibitors against the WIN site of WDR5. These inhibitors selectively block the proliferation of mammalian cells carrying fusions of the MLL1 oncogene. Here, we show that these inhibitors result in the rapid displacement of WDR5 from chromatin in both sensitive (MV4:11) and non-sensitive (K562) cell lines, induce early changes in the distribution of active polymerases at a subset of WDR5-bound genes, and induce global transcript changes that are consistent with induction of the tumor suppressor p53.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platforms:

GPL21290 GPL18573 GPL16791

77 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) WDR5 is a highly-conserved nuclear protein that performs multiple scaffolding functions in the context of chromatin. WDR5 is also a promising target for pharmacological inhibition in cancer, with small molecule inhibitors of an arginine-binding pocket of WDR5 (the "WIN" site) showing efficacy against a range of cancer cell lines in vitro. Efforts to understand WDR5, or establish the mechanism of action of WIN site inhibitors, however, are stymied by its many functions in the nucleus, and a lack of knowledge of the conserved gene networks—if any—that are under its control. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

4 related Platforms

65 Samples

Download data: CSV, NARROWPEAK, TXT

(Submitter supplied) The WIN site of WDR5 is a druggable pocket that is crucial for WDR5 protein function and carries therapeutic potential for treating cancer. This study evaluates the protein interactions affected by small molecule blockade of the WIN site of WDR5. We find that PDPK1 directly binds the WIN site of WDR5, and we investigate this newfound interaction through proteomic, biochemical, and genomic methods.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL24676 GPL20301

20 Samples

Download data: TXT

(Submitter supplied) This study demonstrates the impact of WIN site inhibitors versus WDR5 degradation on H3K4me and transcriptional processes in human Burkitt's lymphoma cells. We use RNA-seq to measure global transcript levels, ChIP-seq to map genomic H3K4me3, and PRO-seq to map genomic polymerase density and primary transcripts. Our data show that WIN site inhibition disables only a specific subset of WDR5 activity, and that H3K4me changes  induced by WDR5 depletion do not explain accompanying transcriptional responses.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platform:

GPL24676

38 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) In this study, we utilized a multi-omics approach to determine the transcriptional, translational, and proteomic responses to WIN Site inhibition in MLL-rearranged leukemia cells via RNA-Seq, Ribo-Seq, and quantitative proteomics, respectively. We also performed both a whole-genome targeting primary CRISPR screen and a secondary CRISPR screen targeting a currated collection of genes to determine genes important for sensitivity to WIN Site inhibition. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL18573 GPL24676

56 Samples

Download data: TXT

(Submitter supplied) WD repeat domain 5 (WDR5) is a core scaffolding component of many multi-protein complexes that perform a variety of critical chromatin-centric processes in the nucleus. WDR5 is component of the mixed lineage leukemia MLL/SET complex and localizes MYC to chromatin tumor-critical target genes. Overexpression of WDR5 promotes oncogenesis in a variety of human cancers that are often associated with poor prognoses. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: TXT

(Submitter supplied) Rhabdoid tumors (RT) are rare and aggressive pediatric tumors that are driven by the loss the tumor suppressor SNF5 (SMARCB1). Here we examine how RT cells respond to small molecule-mediated inhibitors of the “WIN” site of WDR5, a chromatin-associated protein that regulates a specific set of genes linked to protein synthesis. We characterize WDR5 binding in RT cell lines via ChIP-Seq and show that WIN site inhibitor rapidly and comprehensively displaces WDR5 from chromatin in these cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

24 Samples

Download data: TXT

(Submitter supplied) Rhabdoid tumors (RT) are rare and aggressive pediatric tumors that are driven by the loss the tumor suppressor SNF5 (SMARCB1). Here we examine how RT cells respond to small molecule-mediated inhibitors of the “WIN” site of WDR5, a chromatin-associated protein that regulates a specific set of genes linked to protein synthesis. We characterize WDR5 binding in RT cell lines via ChIP-Seq and show that WIN site inhibitor rapidly and comprehensively displaces WDR5 from chromatin in these cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

68 Samples

Download data: TXT

(Submitter supplied) The oncoprotein transcription factor MYC is overexpressed in the majority of human cancers. Key to its oncogenic activity is the ability of MYC to bind chromatin and regulate broad gene expression patterns that drive and maintain the tumorigenic state. The interaction of MYC with chromatin is absolutely dependent on interaction with MAX, but may also be facilitated by additional chromatin-resident proteins such as WDR5. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL20301 GPL18573

42 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL24247

43 Samples

Download data: BED, BIGWIG, BW, GTF, NARROWPEAK

(Submitter supplied) This study describes the transcriptome profiling of day 6 SFEBq embryonic bodies (EBs): 1) WT; 2) Wdr5 KO ; 3) Wdr5 KO with T12h hWDR5 rescue; 4) Wdr5 KO with T48h hWDR5 rescue

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

18 Samples

Download data: GTF

(Submitter supplied) This study describes the binding profile of MAX in mouse embryonic bodies at day 2 (WT, Wdr5 KO, Wdr5 and p53 double knockout)

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

3 Samples

Download data: NARROWPEAK

(Submitter supplied) This study describes the binding profile of WDR5 and H3K4me3 in Wdr5 and p53 double knockout ESC rescued with WDR5WT or WDR5S91KY191F

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

6 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) This study describes time-course chromatin accessibility profiling of mouse ESC and embryonic bodies n Wdr5 and p53 knockout (with or without WT or mutant hWDR5 rescue)

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

16 Samples

Download data: BED, BW, NARROWPEAK

(Submitter supplied) To explore the molecular mechanism underlying OICR-9429-induced WDR5 inhibition in BCa cells, a genome-wide RNA-sequencing was conducted to compare gene expression profiles between OICR-9429 treated T24, UM-UC-3 cells and their control cells

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

4 Samples

Download data: XLSX

(Submitter supplied) We report a comparison of the genome-wide binding patterns of MYC and WDR5, and the effects of a mutation in MYC (WBM) that disrupt the MYC-WDR5 interaction.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

15 Samples

Download data: BED

(Submitter supplied) This study describes the binding profile of WDR5, p53 and H3K4Me3 in mouse embryonic bodies at day 2 (WT, Wdr5 KO, Wdr5 and p53 double knockout)

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

11 Samples

Download data: TXT

(Submitter supplied) This study describes the transcriptome profiling of day 6 SFEBq embryonic bodies (EBs): 1) WT; 2) Wdr5 KO ; 3) Wdr5 KO with T12h hWDR5 rescue; 4) Wdr5 KO with T48h hWDR5 rescue

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

16 Samples

Download data: TXT

(Submitter supplied) This study describes the binding profile of HA-hWDR5 in mouse embryonic bodies with early (T12h) and late (T48h) rescue of HA-hWDR5

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21103

4 Samples

Download data: BW, TXT

(Submitter supplied) This study describes time-course chromatin accessibility profiling of mouse embryonic bodies upon transient mWdr5 deletion with or without hWDR5 rescue

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL21103 GPL17021

22 Samples

Download data: BW